title: 1-(substituted-benzyl)imidazole-2(3H)-thione inhibitors of dopamine beta-hydroxylase.
abstract: Molecular shape and quantitative structure-activity relationship (QSAR) analyses of 52 1-(substituted-benzyl)-imidazole-2(3H)-thione inhibitors of dopamine beta-hydroxylase were carried out. QSARs were developed for sets of 45 and sets of 47 analogues. Molecular shape, as represented by common overlap steric volume and the composite charge density on carbons 3, 4, and 5 of the substituted-benzyl ring are the major inhibition-potency descriptors. Five of the 52 compounds were eliminated prior to analyses on the basis of difficulties in characterizing shape and charge state. Two compounds were outliers. The active conformation deduced in the analyses is a low-energy conformer for both active and inactive inhibitors. This suggests that the intrinsic shape of the molecule due to the selection of X is more important than torsion-angle selection for the bonds between the two rings. The QSARs found in this study have only general similarities to one put forth by Kruse et al. using linear free energy descriptors.
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago 60680.
authors.forename: B J
authors.initials: BJ
authors.lastname: Burke
authors.forename: A J
authors.initials: AJ
authors.lastname: Hopfinger
mesh_terms: D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors*; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D007256:Information Systems; D008968:Molecular Conformation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D013871:Thiones / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D001593:Benzyl Compounds; D007093:Imidazoles; D013871:Thiones; D004299:Dopamine beta-Hydroxylase